In most spontaneously ovulating mammals the corpora lutea formed at ovulation secrets progesterone for approximately 2 weeks. The corporalutea formed at ovulation in the rat secrete progesterone for only a few hours during the estrous cycle. However, a prolonged luteal phase or pseudopregnancy of approximately 2 weeks can be induced in the rat by mating or alternatively, by mechanical or electrical stimulation of the cervix on proestrus. Such stimulation leads to 10 days of daily nocturnal and diurnal surges of prolactin secretion from the pituitary gland. This hormone is responsible for maintenance of the corpus luteum. The cervical stimulus changes the activity of 2 areas of the hypothalamus to initiate these surges. Within the medial preoptic area, it turns off inhibitory neurons for nocturnal and diurnal surges and excites stimulatory neurons for diurnal surges of prolactin. Moreover, the stimulus excites stimulatory neurons for both surges within the dorsomedial-ventromedial areas of the hypothalamus. The prolactin-secretory response to cervical stimulation is further modified by ovarian and uterine input. The ovarian steroids either sensitize or inhibit prolactin secretion while the uterus secretes an unidentified activity which inhibits prolactin secretion directly at the pituitary level. Utilizing radioimmunologic estimates of hormone levels in blood, the chemical identity of the inhibitory and stimulatory input from the hypothalamus to the pituitary gland will be clarified. Moreover, the physiological role, the mechanism of action, and the chemistry of the uterine factor responsible for inhibiting prolactin secretion will be identified. The importance of these studies is that they will describe the nature of the hypothalamic response to a brief exteroceptive stimulus and furthermore will view the non-pregnant uterus as an endocrine organ whoe secretory product modifies pituitary prolactin secreted in response to that stimulus. Such studies also may suggest new methods of regulating fertility.